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活病毒疫苗诱导保护性免疫的早期细胞特征。

The early cellular signatures of protective immunity induced by live viral vaccination.

机构信息

Charité University Medicine CCM, Klinik für Neurologie/NCRC, Berlin, Germany.

出版信息

Eur J Immunol. 2012 Sep;42(9):2363-73. doi: 10.1002/eji.201142306. Epub 2012 Aug 6.

Abstract

Here, we have used primary vaccination of healthy donors with attenuated live yellow fever virus 17D (YFV-17D) as a model to study the generation of protective immunity. In short intervals after vaccination, we analyzed the induction of YFV-17D specific T- and B-cell immunity, bystander activation, dendritic cell subsets, changes in serum cytokine levels, and YFV-17D-specific antibodies. We show activation of innate immunity and a concomitant decline of numbers of peripheral blood T and B cells. An early peak of antigen-specific T cells at day 2, followed by mobilization of innate immune cells, preceded the development of maximal adaptive immunity against YFV-17D at day 14 after vaccination. Interestingly, potent adaptive immunity as measured by high titers of neutralizing YFV-17D-specific antibodies, correlated with early activation and recruitment of YFV-17D-specific CD4(+) T cells and higher levels of sIL-6R. Thus our data might provide new insights into the interplay of innate and adaptive immunity for the induction of protective immunity.

摘要

在这里,我们使用减毒活黄热病毒 17D(YFV-17D)对健康供体进行初级免疫接种作为模型来研究保护性免疫的产生。在接种后的短时间内,我们通过分析 YFV-17D 特异性 T 细胞和 B 细胞免疫、旁观者激活、树突状细胞亚群、血清细胞因子水平变化和 YFV-17D 特异性抗体的产生来研究保护性免疫的产生。我们发现先天免疫被激活,同时外周血 T 细胞和 B 细胞数量减少。在接种后第 14 天产生针对 YFV-17D 的最大适应性免疫之前,第 2 天出现了抗原特异性 T 细胞的早期峰值,随后是先天免疫细胞的动员。有趣的是,如中和 YFV-17D 特异性抗体的高滴度所示,强大的适应性免疫与 YFV-17D 特异性 CD4(+) T 细胞的早期激活和募集以及更高水平的 sIL-6R 相关。因此,我们的数据可能为诱导保护性免疫的先天免疫和适应性免疫的相互作用提供新的见解。

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